tbuckley/cabot-search huggingface dataset:
Monkeypox: Single dose of smallpox vaccine offers 78% protection, UKHSA reports
Authors: Elisabeth Mahase
Journal: BMJ (2022)

A single dose of the MVA-BN (modified vaccinia Ankara-Bavarian Nordic) smallpox vaccine provides around 78% protection against monkeypox 14 days after vaccination, the UK Health Security Agency (UKHSA) has said. 1 The agency's analysis, released as a preprint, looked at monkeypox cases in England and vaccination uptake data from 4 July to 3 November 2022 in the eligible gay, bisexual, and men who have sex with men (GBMSM) cohort.Of 363 cases in this period, eight people had been vaccinated at least 14 days before, and 32 had been vaccinated 0-13 days before.The remaining 323 had not been vaccinated during this outbreak, giving an estimated vaccine effectiveness of 78%.The agency said that this was the "strongest UK evidence yet for the effectiveness of the vaccine," which is sold as Imvanex in the UK and EU and as Jynneos in the US.Currently, the UK is providing a single dose of the vaccine to the GBMSM cohort, as well as to healthcare workers caring for patients with monkeypox and people who have already had close contact with someone with monkeypox. 2Steve Russell, NHS national director of vaccinations and screening, said, "More than 55 000 doses of the monkeypox vaccine have been delivered so far.While the risk of monkeypox remains low, we urge anyone eligible to come forward to get their vaccination."Since the outbreak began in May 2022 the UK has reported 3720 monkeypox cases up to 21 November. 3 Vaccine uptake among eligible GBMSM increased steadily from July, reaching 47% by 9 October.Jamie Lopez-Bernal, consultant epidemiologist at the UKHSA, said, "While monkeypox cases are low it remains vital to stay alert to the risks.We now know that a single vaccine dose provides strong protection against monkeypox, which shows just how important vaccination is to protect yourself and others.A second dose is expected to offer even greater and longer lasting protection."The UKHSA has said that it will continue to investigate the duration of protection from a single dose and two doses of the vaccine. 1
John Launer: On being stuck
Authors: John Launer
Journal: BMJ (2022)

A lot of my work consists of supervision-not in the sense of training and managing people or telling them what to do, but instead offering a reflective space for them to consider their thornier problems.This kind of supervision is regarded as essential in some other professions dealing in complexity, such as social work.In general practice, and medicine more widely, it's far less common beyond the training years than it should be.Recently I offered this kind of supervision to a young GP who felt stuck with a patient.He was seeing a woman with multiple symptoms that had eluded diagnosis or successful treatment.He was trying to help the patient see things in a different light-as the consequence of life experiences perhaps or in a way that might be tackled through her own strengths.Nothing he did or said seemed to make a difference.This is of course the familiar stuff of general practice.
Low alcohol consumption influences outcomes in individuals with alcohol-related compensated cirrhosis in a French multicenter cohort
Authors: Alexandre Louvet, Valérie Bourcier, Isabelle Archambeaud, Louis d’Alteroche, Cendrine Chaffaut, Frédéric Oberti, Christophe Moreno, Dominique Roulot, Thông Dao, Romain Moirand, Jean-Charles Duclos-Vallée, Odile Goria, Eric Nguyen-Khac, Stanislas Pol, Nicolas Carbonell, Jérôme Gournay, Laure Elkrief, Isabelle Fouchard-Hubert, Sylvie Chevret, Nathalie Ganne-Carrié, Nathalie Ganne-Carrié, Valérie Bourcier, Cendrine Chaffaut, Sylvie Chevret, Isabelle Archambeaud, Jérôme Gournay, None Louis d’Alteroche, Laure Elkrief, Frédéric Oberti, Isabelle Fouchard-Hubert, Dominique Roulot, Christophe Moreno, Alexandre Louvet, Thông Dao, Romain Moirand, Jean-Charles Duclos-Vallée, Odile Goria, Eric Nguyen-Khac, Stanislas Pol, Nicolas Carbonell, Jean-Marie Péron, Victor de Lédinghen, Violaine Ozenne, Jean Henrion, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski
Journal: Journal of Hepatology (2022)
Progress Toward Global Eradication of Dracunculiasis — Worldwide, January 2021–June 2022
Authors: Donald R. Hopkins, Adam J. Weiss, Sarah Yerian, Sarah G.H. Sapp, Vitaliano A. Cama
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Dracunculiasis (Guinea worm disease), caused by the parasite Dracunculus medinensis, is acquired by drinking water containing small crustacean copepods (water fleas) infected with D. medinensis larvae. Recent evidence suggests that the parasite also appears to be transmitted by eating fish or other aquatic animals. About 1 year after infection, the worm typically emerges through the skin on a lower limb of the host, causing pain and disability (1). No vaccine or medicine is available to prevent or treat dracunculiasis. Eradication relies on case containment* to prevent water contamination and other interventions to prevent infection, including health education, water filtration, treatment of unsafe water with temephos (an organophosphate larvicide), and provision of safe drinking water (1,2). CDC began worldwide eradication efforts in October 1980, and in 1984 was designated by the World Health Organization (WHO) as the technical monitor of the Dracunculiasis Eradication Program (1). In 1986, with an estimated 3.5 million cases† occurring annually in 20 African and Asian countries§ (3), the World Health Assembly called for dracunculiasis elimination. The Guinea Worm Eradication Program (GWEP),¶ led by The Carter Center and supported by partners that include WHO, UNICEF, and CDC, began assisting ministries of health in countries with endemic disease. In 2021, a total of 15 human cases were identified and three were identified during January-June 2022. As of November 2022, dracunculiasis remained endemic in five countries (Angola, Chad, Ethiopia, Mali, and South Sudan); cases reported in Cameroon were likely imported from Chad. Eradication efforts in these countries are challenged by infection in animals, the COVID-19 pandemic, civil unrest, and insecurity. Animal infections, mostly in domestic dogs, some domestic cats, and in Ethiopia, a few baboons, have now surpassed human cases, with 863 reported animal infections in 2021 and 296 during January-June 2022. During the COVID-19 pandemic all national GWEPs remained fully operational, implementing precautions to ensure safety of program staff members and community members. In addition, the progress toward eradication and effectiveness of interventions were reviewed at the 2021 and 2022 annual meetings of GWEP program managers, and the 2021 meeting of WHO's International Commission for the Certification of Dracunculiasis Eradication. With only 15 human cases identified in 2021 and three during January-June 2022, program efforts appear to be closer to reaching the goal of eradication. However, dog infections and impeded access because of civil unrest and insecurity in Mali and South Sudan continue to be the greatest challenges for the program. This report describes progress during January 2021-June 2022 and updates previous reports (2,4).
<i>QuickStats</i>: Drug Overdose Death Rates* Among Persons Aged ≥15 Years, by Age Group and Urban-Rural Status<sup>†</sup> — National Vital Statistics System, United States, 2020
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Deaths per 100,000 population Age group, yrs Urban Rural * Deaths per 100,000 population; 95% CIs indicated by error bars.Drug overdose deaths were identified using the International Classification of Diseases, Tenth Revision underlying cause-of-death codes X40-X44 (unintentional), X60-X64 (suicide), X85 (homicide), or Y10-Y14 (undetermined intent).† Urban-rural status is based on county of residence using the National Center for Health Statistics Urban-Rural Classification Scheme for Counties.https://www.cdc.gov/nchs/data/series/sr_02/sr02_166.pdfDuring 2020, death rates for drug overdose causes were higher in urban areas than in rural areas for those aged 15-24 years (17.2 compared with 13.3), 45-64 years (43.4 compared with 33.5), and ≥65 years (10.0 compared with 6.2).Among adults aged 25-44, drug overdose death rates were not significantly different between urban and rural areas (50.3 compared with 51.6).Drug overdose death rates were lower for adults aged ≥65 years compared with other age groups in both urban and rural areas.
Abortion Surveillance — United States, 2020
Authors: Katherine Kortsmit, Antoinette T. Nguyen, Michele G. Mandel, Elizabeth Clark, Lisa M. Hollier, Jessica Rodenhizer, Maura K. Whiteman
Journal: MMWR Surveillance Summaries (2022)

CDC conducts abortion surveillance to document the number and characteristics of women obtaining legal induced abortions and number of abortion-related deaths in the United States.
Clinical and genetic characterization of Epstein-Barr virus–associated T/NK-cell lymphoproliferative diseases
Authors: Hui Luo, Dan Liu, Wenbing Liu, Jin Jin, Xiaoman Bi, Peiling Zhang, Jia Gu, Miao Zheng, Min Xiao, Xin Liu, Jianfeng Zhou, Qian-Fei Wang
Journal: Journal of Allergy and Clinical Immunology (2022)
A highly potent small-molecule antagonist of exportin-1 selectively eliminates CD44+CD24- enriched breast cancer stem-like cells
Authors: Caigang Liu, Yixiao Zhang, Jiujiao Gao, Qi Zhang, Lisha Sun, Qingtian Ma, Xinbo Qiao, Xinnan Li, Jinchi Liu, Jiawen Bu, Zhan Zhang, Ling Han, Dongyu Zhao, Yongliang Yang
Journal: Drug Resistance Updates (2022)

Breast cancer stem-like cells (BCSCs) have been suggested as the underlying cause of tumor recurrence, metastasis and drug resistance in triple-negative breast cancer (TNBC). Here, we report the discovery and biological evaluation of a highly potent small-molecule antagonist of exportin-1, LFS-1107. We ascertained that exportin-1 (also named as CRM1) is a main cellular target of LFS-1107 by nuclear export functional assay, bio-layer interferometry binding assay and C528S mutant cell line. We found that LFS-1107 significantly inhibited TNBC tumor cells at low-range nanomolar concentration and LFS-1107 can selectively eliminate CD44+CD24- enriched BCSCs. We demonstrated that LFS-1107 can induce the nuclear retention of Survivin and consequent strong suppression of STAT3 transactivation abilities and the expression of downstream stemness regulators. Administration of LFS-1107 can strongly inhibit tumor growth in mouse xenograft model and eradicate BCSCs in residual tumor tissues. Moreover, LFS-1107 can significantly ablate the patient-derived tumor organoids (PDTOs) of TNBC as compared to a few approved cancer drugs. Lastly, we revealed that LFS-1107 can enhance the killing effects of chemotherapy drugs and downregulate multidrug resistance related protein targets. These new findings provide preclinical evidence of defining LFS-1107 as a promising therapeutic agent to deplete BCSCs for the treatment of TNBC.
Placebo response in objective and subjective measures of hypersomnia in randomized clinical trials on obstructive sleep apnea. A systematic review and meta-analysis
Authors: Gonzalo Labarca, Rodrigo Montenegro, Grace Oscullo, Mario Henriquez-Beltran, Juan P. Uribe, Jose Daniel Gómez-Olivas, Alberto Garcia-Ortega, Miguel Ángel Martínez-García
Journal: Sleep Medicine Reviews (2022)
Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer
Authors: N.C. Turner, C. Swift, B. Jenkins, L. Kilburn, M. Coakley, M. Beaney, L. Fox, K. Goddard, I. Garcia-Murillas, P. Proszek, P. Hall, C. Harper-Wynne, T. Hickish, S. Kernaghan, I.R. Macpherson, A.F.C. Okines, C. Palmieri, S. Perry, K. Randle, C. Snowdon, H. Stobart, A.M. Wardley, D. Wheatley, S. Waters, M.C. Winter, M. Hubank, S.D. Allen, J.M. Bliss, None S. Chan, A. Armstrong, F. Raja, P. Schmid, A. Tutt, R. Roux, S. Cleator
Journal: Annals of Oncology (2022)

Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected [ctDNA positive (ctDNA+)].c-TRAK TN, a multicentre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three-monthly blood sampling to 12 months (18 months if samples were missed due to coronavirus disease), and ctDNA+ patients were randomised 2 : 1 to intervention : observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16 September 2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were (i) ctDNA detection rate and (ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961).Two hundred and eight patients registered between 30 January 2018 and 06 December 2019, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27.3% (44/161, 95% confidence interval 20.6% to 34.9%). Seven patients relapsed without prior ctDNA detection. Forty-five patients entered the therapeutic component (intervention n = 31; observation n = 14; one observation patient was re-allocated to intervention following protocol amendment). Of patients allocated to intervention, 72% (23/32) had metastases on staging at the time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance.c-TRAK TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes.
Brainstem circuits encoding start, speed, and duration of swimming in adult zebrafish
Authors: Eva M. Berg, Leander Mrowka, Maria Bertuzzi, David Madrid, Laurence D. Picton, Abdeljabbar El Manira
Journal: Neuron (2022)

The flexibility of locomotor movements requires an accurate control of their start, duration, and speed. How brainstem circuits encode and convey these locomotor parameters remains unclear. Here, we have combined in vivo calcium imaging, electrophysiology, anatomy, and behavior in adult zebrafish to address these questions. We reveal that the detailed parameters of locomotor movements are encoded by two molecularly, topographically, and functionally segregated glutamatergic neuron subpopulations within the nucleus of the medial longitudinal fasciculus. The start, duration, and changes of locomotion speed are encoded by vGlut2+ neurons, whereas vGlut1+ neurons encode sudden changes to high speed/high amplitude movements. Ablation of vGlut2+ neurons compromised slow-explorative swimming, whereas vGlut1+ neuron ablation impaired fast swimming. Our results provide mechanistic insights into how separate brainstem subpopulations implement flexible locomotor commands. These two brainstem command subpopulations are suitably organized to integrate environmental cues and hence generate flexible swimming movements to match the animal's behavioral needs.
Mucosal delivery of nanovaccine strategy against COVID-19 and its variants
Authors: Junwoo Lee, Dongwoo Khang
Journal: Acta Pharmaceutica Sinica B (2022)

Despite the global administration of approved COVID-19 vaccines (e.g., ChAdOx1 nCoV-19®, mRNA-1273®, BNT162b2®), the number of infections and fatalities continue to rise at an alarming rate because of the new variants such as Omicron and its subvariants. Including COVID-19 vaccines that are licensed for human use, most of the vaccines that are currently in clinical trials are administered via parenteral route. However, it has been proven that the parenteral vaccines do not induce localized immunity in the upper respiratory mucosal surface, and administration of the currently approved vaccines does not necessarily lead to sterilizing immunity. This further supports the necessity of a mucosal vaccine that blocks the main entrance route of COVID-19: nasal and oral mucosal surfaces. Understanding the mechanism of immune regulation of M cells and dendritic cells and targeting them can be another promising approach for the successful stimulation of the mucosal immune system. This paper reviews the basic mechanisms of the mucosal immunity elicited by mucosal vaccines and summarizes the practical aspects and challenges of nanotechnology-based vaccine platform development, as well as ligand hybrid nanoparticles as potentially effective target delivery agents for mucosal vaccines.
Clinical Relevance of Random Biopsies From the Esophagogastric Junction After Complete Eradication of Barrett’s Esophagus is Low
Authors: Charlotte N. Frederiks, Sanne N. van Munster, Esther A. Nieuwenhuis, Lorenza Alvarez Herrero, Alaa Alkhalaf, Boudewijn E. Schenk, Erik J. Schoon, Wouter L. Curvers, Arjun D. Koch, Pieter-Jan F. de Jonge, Thjon Tang, Wouter B. Nagengast, Jessie Westerhof, Martin H.M.G. Houben, Jacques J.G.H.M. Bergman, Roos E. Pouw, Bas L.A.M. Weusten
Journal: Clinical Gastroenterology and Hepatology (2022)

Although random histological sampling from the esophagogastric junction (EGJ) after complete eradication of Barrett's esophagus (BE) is recommended, its clinical relevance is questionable. This study aimed to assess the incidence and long-term outcomes of findings from random EGJ biopsies in a nationwide cohort with long-term follow-up.We included all patients with successful endoscopic eradication therapy (EET), defined as complete endoscopic eradication of all visible BE (CE-BE), for early BE neoplasia from the Dutch registry. Patients were treated and followed-up in 9 expert centers according to a joint protocol. Outcomes included the incidence of intestinal metaplasia (IM) at the EGJ (EGJ-IM) and the association between IM and visible (dysplastic) BE recurrence.A total of 1154 patients were included with a median follow-up of 43 months (interquartile range, 22-69 months). At the time of CE-BE, persisting EGJ-IM was found in 7% of patients (78/1154), which was reproduced during further follow-up in 46% of patients (42/78). No significant association existed between persisting EGJ-IM at CE-BE and recurrent non-dysplastic or dysplastic BE (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.63-2.13 and HR, 0.73; 95% CI, 0.17-3.06, respectively). Among patients with no EGJ-IM at the time of CE-BE (1043/1154; 90%), EGJ-IM recurred in 7% (72/1043) after a median of 21 months (interquartile range, 15-36 months), and was reproduced during further follow-up in 26% of patients (19/72). No association was found between recurrent EGJ-IM and non-dysplastic or dysplastic recurrence (HR, 1.18; 95% CI, 0.67-2.06 and HR, 0.27; 95% CI, 0.04-1.96, respectively).Because EGJ-IM was not associated with a higher risk for recurrent disease, we recommend to consider abandoning random EGJ sampling after successful EET, under the condition that care is provided in expert centers, and the esophagus, including the EGJ, is carefully inspected (Netherlands Trial Register, NL7309).
The path to healthy ageing in China: a Peking University–Lancet Commission
Authors: Xinxin Chen, John Giles, Yao Yao, Winnie Yip, Qinqin Meng, Lisa Berkman, He Chen, Xi Chen, Jin Feng, Zhanlian Feng, Elena Glinskaya, Jinquan Gong, Perry Hu, Haidong Kan, Xiaoyan Lei, Xiao Liu, Andrew Steptoe, Gewei Wang, Harold Wang, Huali Wang, Xiaoyu Wang, Yafeng Wang, Li Yang, Luxia Zhang, Quan Zhang, Jing Wu, Zunyou Wu, John Strauss, James Smith, Yaohui Zhao
Journal: The Lancet (2022)
Ultrasmall iron-quercetin metal natural product nanocomplex with antioxidant and macrophage regulation in rheumatoid arthritis
Authors: Zhihui Han, Xiang Gao, Yuanjie Wang, Shuning Cheng, Xiaoyan Zhong, Yong Xu, Xiaozhong Zhou, Zengli Zhang, Zhuang Liu, Liang Cheng
Journal: Acta Pharmaceutica Sinica B (2022)

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.
慢性腰背痛的非药物治疗—如果根据患者需要进行调整，督导下体育锻炼是有效的
Authors: Maurits, van, 张扬红
Journal: BMJ (2008)

在发达国家，腰背痛是个重要的健康问题。这些患者通常均在初级卫生保健机构接受治疗。约有49％-70％的人终生为腰背痛困扰，12％-30％的人在某个时期患病^[1]。慢性腰背痛的处理方法在不同国家甚至同一个国家的医疗机构亦有很大差异。在近期BMJ，Little及其同事发表的随机对照试验对英格兰64个全科医疗机构。
Corrigendum to: Palliative care and end-of-life care in adults with malignant brain tumors
Authors: Johan A F Koekkoek, Pim B van der Meer, Andrea Pace, Caroline Hertler, Rebecca Harrison, Heather E Leeper, Deborah A Forst, Rakesh Jalali, Kathy Oliver, Jennifer Philip, Martin J B Taphoorn, Linda Dirven, Tobias Walbert
Journal: Neuro-Oncology (2022)
Ethics Consultation—A Blind Spot of Philosophy in Bioethics?
Authors: Dagmar Schmitz, Marcus Duewell
Journal: The American Journal of Bioethics (2022)

"Ethics Consultation—A Blind Spot of Philosophy in Bioethics?." The American Journal of Bioethics, 22(12), pp. 47–48This article refers to:The Place of Philosophy in Bioethics Today Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.
The Mutual Benefit of the Integration of Philosophy and Bioethics – Our Experience from an Interdisciplinary Research Project on (Epi-)Genome Editing
Authors: Karla Karoline Sonne Kalinka Alex, Eva C. Winkler
Journal: The American Journal of Bioethics (2022)

Click to increase image sizeClick to decrease image sizeThis article refers to:The Place of Philosophy in Bioethics Today Additional informationFundingThe work on this commentary was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft) [409799774] as part of the project "COMParative ASSessment of Genome- and Epigenome Editing in Medicine: Ethical, Legal and Social Implications (COMPASS-ELSI)" and, during the second funding period: COMPASS-ELSI 2.0.